rs3895234

Variant names:

• chr11-35306278-A-G
• rs3895234
• NM_004171.4:c.562-36T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004171.4(SLC1A2):​c.562-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,557,256 control chromosomes in the GnomAD database, including 47,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3993 hom., cov: 31)
  • Exomes 𝑓: 0.24 (43157 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.03

Genes affected

SLC1A2 (HGNC:10940): (solute carrier family 1 member 2) This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-35306278-A-G is Benign according to our data. Variant chr11-35306278-A-G is described in ClinVar as [Benign]. Clinvar id is 1332976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.562-36T>C		intron_variant	Intron 4 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.562-36T>C		intron_variant	Intron 4 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33222 AN: 151680 Hom.: 3976 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.237 AC: 56272 AN: 237210 AF XY: 0.230

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.213

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.254

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.243 AC: 341855 AN: 1405460 Hom.: 43157 Cov.: 22 AF XY: 0.239 AC XY: 166602 AN XY: 697576

Gnomad4 AFR exome AF: 0.139 AC: 4458 AN: 31986

Gnomad4 AMR exome AF: 0.296 AC: 12550 AN: 42364

Gnomad4 ASJ exome AF: 0.213 AC: 5319 AN: 25012

Gnomad4 EAS exome AF: 0.274 AC: 10661 AN: 38874

Gnomad4 SAS exome AF: 0.104 AC: 8570 AN: 82472

Gnomad4 FIN exome AF: 0.318 AC: 16201 AN: 51000

Gnomad4 NFE exome AF: 0.252 AC: 269985 AN: 1070140

Gnomad4 Remaining exome AF: 0.225 AC: 13045 AN: 58030

GnomAD4 genome AF: 0.219 AC: 33268 AN: 151796 Hom.: 3993 Cov.: 31 AF XY: 0.221 AC XY: 16368 AN XY: 74166

Gnomad4 AFR AF: 0.136 AC: 0.135698 AN: 0.135698

Gnomad4 AMR AF: 0.282 AC: 0.281508 AN: 0.281508

Gnomad4 ASJ AF: 0.205 AC: 0.204559 AN: 0.204559

Gnomad4 EAS AF: 0.215 AC: 0.215116 AN: 0.215116

Gnomad4 SAS AF: 0.0912 AC: 0.0912303 AN: 0.0912303

Gnomad4 FIN AF: 0.320 AC: 0.319527 AN: 0.319527

Gnomad4 NFE AF: 0.251 AC: 0.250611 AN: 0.250611

Gnomad4 OTH AF: 0.221 AC: 0.220644 AN: 0.220644

Alfa AF: 0.225 Hom.: 753

Bravo AF: 0.216

Asia WGS AF: 0.187 AC: 648 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Developmental and epileptic encephalopathy, 41 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.098
DANN	Benign	0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3895234; hg19: chr11-35327825; COSMIC: COSV53519634; COSMIC: COSV53519634;